Fibronectin is a key component of the extracellular matrix whose abundance and organization depend on both environmental conditions and intracellular signaling. In this study we show that oxygen tension modifies the response of extravillous trophoblasts to TGF-β1 and thereby controls fibronectin output and matrix dependent cell behavior. TGF-β1 increased fibronectin transcripts and protein through SMAD3, p38 and AKT, while hypoxia altered this response by reducing fibronectin protein despite preserved mRNA and by shifting downstream phosphorylation toward SMAD3, ERK and p38 with reduced AKT activity. These changes influenced functional outcomes: fibronectin rich conditions and TGF-β1 suppressed invasion and supported endothelial-like organization, and interference with fibronectin integrin binding preserved invasiveness and prevented network formation. Analysis of placental tissue showed that the spatial pattern of fibronectin expression differs in severe preeclampsia, where fibronectin appears earlier along the trophoblast trajectory compared with normal pregnancy. Together, these findings define how oxygen and TGF-β1 jointly regulate fibronectin and trophoblast behavior, while descriptive observations in human placental tissue provide histological context consistent with these cellular responses and suggest a potential role for matrix-associated signaling in severe preeclampsia.

Digital health has emerged as a key tool in prenatal care, facilitating access to information and improving communication between pregnant women and healthcare professionals. In Chile, the Chile Crece Contigo (ChCC) platform provides digital resources to support pregnancy and early childhood. However, there are limitations to its use. AIM:To explore the profile of pregnant women who use the ChCC website and compare it with those who do not, identifying factors associated with its use. METHODS:A quantitative, observational, and cross-sectional study was conducted with 146 pregnant women attending Family Health Centers (CESFAM) in the Metropolitan and Valparaíso regions. Sociodemographic and obstetric variables were analyzed based on the use of the ChCC website. The chi-square test was used for statistical comparisons, considering p<0.05 as significant. RESULTS:A total of 79.5% of the participants reported not visiting the website. ChCC users were predominantly under 35 years old (93%), had technical or university education (66.6%), and were unemployed or students (66.6%). In contrast, non-users had a higher prevalence of overweight/obesity (81%), had completed secondary education (44.8%), and were employed (50.9%). Significant differences were observed in website usage according to educational level and geographic area (p= 0.036). CONCLUSIONS:Use of the ChCC platform is associated with sociodemographic factors, particularly educational level and body mass index. Improving the dissemination and accessibility of the website is essential to promote its use among groups with lower educational attainment and altered nutritional status.

Maternal physiological hypercholesterolemia (MPH; total cholesterol (TC)≤280 mg/dL) occurs during pregnancy to support fetal growth. When TC exceeds this threshold, this condition is recognized as maternal supraphysiological hypercholesterolemia (MSPH), which is associated with endothelial dysfunction in the maternal and fetoplacental vasculature. Placenta-derived extracellular vesicles (EVs), which mediate intercellular communication during pregnancy, may contribute to MSPH by affecting endothelial cells. Aim To characterize EVs isolated from MPH and MSPH term placentas and assess their effects on endothelial function in vitro. Methods EVs from term MPH (n = 10) and MSPH (n = 10) placental explants were purified by differential ultracentrifugation. EVs were characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy, and analysis of protein markers and content. MPH- and MSPH-EVs were labeled to assess their uptake by endothelial cells (HMEC-1). Their effects on angiogenesis, endothelial activation, endothelial nitric oxide (NO) synthase (eNOS) protein expression and NO levels were evaluated. Results The concentration and morphology of placental EVs from MPH and MSPH were comparable. When HMEC-1 were exposed to placenta-derived EVs, MSPH-EVs increased angiogenic capacity. Intercellular adhesion molecule-1 (ICAM-1) expression was induced regardless of whether vesicles were originated from MPH or MSPH placentas. No differences were observed in eNOS expression or NO production when cells were incubated with placenta-derived EVs from both conditions. Conclusion In our in vitro model, MSPH placenta-derived EVs adjusted angiogenesis but did not alter eNOS expression or activity in endothelial cells. Our findings suggest that placental EVs could have a protective role in the NO-associated endothelial dysfunction described in MSPH pregnancies.

Every Latin square of prime power order q is uniquely described by a local permutation polynomial (LPP) in the polynomial ring 𝔽_q[x,y]. Despite this equivalence, one may find in the literature only some preliminary results on the relationship among Latin squares and LPPs. This paper delves into this topic by showing how the coefficients of any LPP are identified with the zeros of an algebraic set over 𝔽_q. This allows for an algebraic description of all Latin squares of order q by means of a unique polynomial in 𝔽_q[x,y], whose coefficients satisfy the constraints defined by the algebraic set under consideration. In order to make much easier the construction of this polynomial, we also deal with the natural translation to LPPs of both notions of reduced and isotopic Latin squares. Our algebraic approach is readily adapted to identify both types of Latin squares. All of the above is constructively illustrated for q∈{4,5}. We finish our study with the natural translation to LPPs of both notions of complete mappings and orthomorphisms of quasigroups, showing their relationship with transversals and isotopisms of Latin squares.

Background ApoER2/LRP8 is a receptor highly expressed in the placenta; however, its physiological role in this organ is little known. Reelin, an ApoER2 ligand, is an extracellular glycoprotein that participates in neuronal polarization, migration and differentiation, hence having a central role in the central nervous system (CNS) development. Upon binding to ApoER2, Reelin triggers a complex signaling pathway that regulates cytoskeleton dynamics, gene expression and transcript translation. This paper aimed to determine whether the ApoER2/Reelin signaling pathway has roles in cellular processes related to placentation. Results We characterized the Reelin-ApoER2 system using first-trimester extravillous trophoblast (EVT) cell lines. The receptor is present at the cell surface and in the nucleus. EVT cells Swan 71 responded to Reelin exposure by activating the PI3K-Akt and increasing ApoER2 levels. Additionally, a dual role of Reelin through PI3K was established in these cells, as it enhanced trophoblastic migration at 2% O 2 (to mimic the hypoxic physiologic conditions of trophoblastic migration) and its differentiation to an endothelial-like phenotype at 21% O 2 . Migration was also stimulated, independent of PI3K, when cells were exposed to normoxic culture conditions (21% of O 2 ) or chemically induced hypoxia (by CoCl 2 ). We propose that physiologically, during the first trimester, Reelin, together with its ApoER2 receptor, could act by stimulating trophoblastic migration and differentiation. Interestingly, Reelin also modulated hypoxia-inducible factor HIF1-α levels. Both ApoER2 and Reelin were detected in human term placentas from normal and preeclampsia with severe features (PE-SF) pregnancies. Reelin plasma levels were lower in severe PE patients already in the first semester of pregnancy, before the appearance of PE symptoms. Conclusions Reelin could be involved in placentation, playing roles in EVT migration and differentiation. The reduction in maternal Reelin levels detected at early pregnancy could be a potential biomarker for PE.

INTRODUCTION:The mechanisms leading to proper placentation are not fully understood. Extravillous trophoblasts (EVTs) are crucial for placentation through invasion and vascular remodeling, which, when impaired, promote a poor placentation. How autophagy could regulate EVTs function and the study of regulators of these processes, such as oxidized low-density lipoproteins (ox-LDL), could contribute to better understand events associated with pregnancy complications related to abnormal placental development, such as preeclampsia (PE). AIM:To investigate the role of autophagy and oxidized LDL (ox-LDL) in invasion and endothelial-like phenotype acquisition of a model of EVTs, as well as to determine the levels of autophagy flux markers in control and PE placentas. METHODS:Invasion and endothelial-like phenotype acquisition assays were performed in a cell line model of first trimester EVTs: HTR-8/SVneo cultured in normoxia (oxygen concentration of 20 %), in the absence or the presence of the autophagy inhibitor bafilomycin or/and ox-LDL. Markers of autophagic flux were evaluated in human term placentas. RESULTS:Autophagy is essential for EVTs to acquire an endothelial-like phenotype but does not affect invasion. Conversely, ox-LDL decreases invasion and reticular structures formation, independent of autophagy. At pregnancy term, the levels of the autophagy markers LC3 and p62 are deregulated in the trophoblast cells of PE placentas. CONCLUSION:Autophagy is necessary for proper endothelial-like phenotype acquisition in HTR-8/SVneo cultured in normoxia, and ox-LDL impairs this process as well as the invasion of EVTs by a mechanism independent of autophagy. Changes in autophagy and/or in the concentration of ox-LDL could affect placental vascular remodeling.

Let \begin{document}$ p $\end{document} be a prime and \begin{document}$ \mathbb{F}_p $\end{document} the finite field with \begin{document}$ p $\end{document} elements. We show how, when given an superelliptic curve \begin{document}$ Y^n+f(X) \in \mathbb{F}_p[X,Y] $\end{document} and an approximation to \begin{document}$ (v_0,v_1) \in \mathbb{F}_p^2 $\end{document} such that \begin{document}$ v_1^n = -f(v_0) $\end{document}, one can recover \begin{document}$ (v_0,v_1) $\end{document} efficiently, if the approximation is good enough. As consequence we provide an upper bound on the number of roots of such bivariate polynomials where the roots have certain restrictions. The results has been motivated by the predictability problem for non-linear pseudorandom number generators and, other potential applications to cryptography.

The Developmental Origins of Health and Disease hypothesis sustains that exposure to different stressors during prenatal development prepares the offspring for the challenges to be encountered after birth. We studied the gestational period as a particularly vulnerable window where different stressors can have strong implications for fetal programming of the offspring's life-long metabolic status via alterations of specific placentally expressed nutrient transporters. To study this mechanism, we used a murine prenatal stress model, human preeclampsia, early miscarriage, and healthy placental tissue samples, in addition to in vitro models of placental cells. In stressed mice, placental overexpression of L-type amino acid transporter 1 (Lat1) and subsequent global placental DNA hypermethylation was accompanied by fetal and adult hypothalamic dysregulation in global DNA methylation and gene expression as well as long-term metabolic abnormalities exclusively in female offspring. In human preeclampsia, early miscarriage, and under hypoxic conditions, placental LAT1 was significantly upregulated, leading to increased methionine uptake and global DNA hypermethylation. Remarkably, subgroups of healthy term placentas with high expression of stress-related genes presented increased levels of placental LAT1 mRNA and protein, DNA and RNA hypermethylation, increased methionine uptake capacity, one-carbon metabolic pathway disruption, higher methionine concentration in the placenta and transport to the fetus specifically in females. Since LAT1 mediates the intracellular accumulation of methionine, global DNA methylation, and one-carbon metabolism in the placenta, our findings hint at a major sex-specific global response to a variety of prenatal stressors affecting placental function, epigenetic programming, and life-long metabolic disease and provide a much-needed insight into early-life factors predisposing females/women to metabolic disorders.

Background The World Federation of Obesity warns that the main health problem of the next decade will be childhood obesity. It is known that factors such as gestational obesity produce profound effects on fetal programming and are strong predictors of overweight and obesity in children. Therefore, establishing healthy eating behaviors during pregnancy is the key to the primary prevention of the intergenerational transmission of obesity. Mobile health (mHealth) programs are potentially more effective than face-to-face interventions, especially during a public health emergency such as the COVID-19 outbreak. Objective This study aims to evaluate the effectiveness of an mHealth intervention to reduce excessive weight gain in pregnant women who attend family health care centers. Methods The design of the intervention corresponds to a classic randomized clinical trial. The participants are pregnant women in the first trimester of pregnancy who live in urban and semiurban areas. Before starting the intervention, a survey will be applied to identify the barriers and facilitators perceived by pregnant women to adopt healthy eating behaviors. The dietary intake will be estimated in the same way. The intervention will last for 12 weeks and consists of sending messages through a multimedia messaging service with food education, addressing the 3 domains of learning (cognitive, affective, and psychomotor). Descriptive statistics will be used to analyze the demographic, socioeconomic, and obstetric characteristics of the respondents. The analysis strategy follows the intention-to-treat principle. Logistic regression analysis will be used to compare the intervention with routine care on maternal pregnancy outcome and perinatal outcome. Results The recruitment of study participants began in May 2022 and will end in May 2023. Results include the effectiveness of the intervention in reducing the incidence of excessive gestational weight gain. We also will examine the maternal-fetal outcome as well as the barriers and facilitators that influence the weight gain of pregnant women. Conclusions Data from this effectiveness trial will determine whether mami-educ successfully reduces rates of excessive weight gain during pregnancy. If successful, the findings of this study will generate knowledge to design and implement personalized prevention strategies for gestational obesity that can be included in routine primary care. Trial Registration ClinicalTrials.gov NCT05114174; https://clinicaltrials.gov/ct2/show/NCT05114174 International Registered Report Identifier (IRRID) DERR1-10.2196/44456

Maternal physiological hypercholesterolemia MPH, maternal total cholesterol (TC) levels at term of pregnancy <280 mg/dL) occurs to assure fetal development. Maternal supraphysiological hypercholesterolemia (MSPH, TC levels >280 mg/dL) is a pathological condition associated with maternal, placental, and fetal endothelial dysfunction and early neonatal atherosclerosis development. Small extracellular vesicles (sEVs) are delivered to the extracellular space by different cells, where they modulate cell functions by transporting active signaling molecules, including proteins and miRNA.Aim: To determine whether sEVs from MSPH women could alter the function of endothelial cells (angiogenesis, endothelial activation and nitric oxide synthesis capacity).Methods: This study included 24 Chilean women (12 MPH and 12 MSPH). sEVs were isolated from maternal plasma and characterized by sEV markers (CD9, Alix and HSP70), nanoparticle tracking analysis, transmission electron microscopy, and protein and cholesterol content. The endothelial cell line HMEC-1 was used to determine the uptake of labeled sEVs and the effects of sEVs on cell viability, endothelial tube formation, endothelial cell activation, and endothelial nitric oxide expression and function.Results: In MSPH women, the plasma concentration of sEVs was increased compared to that in MPH women. MSPH-sEVs were highly taken up by HMEC-1 cells and reduced angiogenic capacity and the expression and activity of eNOS without changing cell viability or endothelial activation compared to MPH-sEVs. Conclusion: sEVs from MSPH women impair angiogenesis and nitric oxide synthesis in endothelial cells, which could contribute to MSPH-associated endothelial dysfunction.

Pregnancies are a critical window period for environmental influences over the mother and the offspring. There is a growing body of evidence associating indoor and outdoor air pollution exposure to adverse pregnancy outcomes such as preterm birth and hypertensive disorders of pregnancy. Particulate matter (PM) could trigger oxi-inflammation and could also reach the placenta leading to placental damage with fetal consequences. The combination of strategies such as risk assessment, advise about risks of environmental exposures to pregnant women, together with nutritional strategies and digital solutions to monitor air quality can be effective in mitigating the effects of air pollution during pregnancy.

Identification of genetic modulators of lysosomal enzyme activities and glycosphingolipids (GSLs) may facilitate the development of therapeutics for diseases in which they participate, including Lysosomal Storage Disorders (LSDs). To this end, we used a systems genetics approach: we measured 11 hepatic lysosomal enzymes and many of their natural substrates (GSLs), followed by modifier gene mapping by GWAS and transcriptomics associations in a panel of inbred strains. Unexpectedly, most GSLs showed no association between their levels and the enzyme activity that catabolizes them. Genomic mapping identified 30 shared predicted modifier genes between the enzymes and GSLs, which are clustered in three pathways and are associated with other diseases. Surprisingly, they are regulated by ten common transcription factors, and their majority by miRNA-340p. In conclusion, we have identified novel regulators of GSL metabolism, which may serve as therapeutic targets for LSDs and may suggest the involvement of GSL metabolism in other pathologies.

With recent advances in genomic sequencing, the importance of taking the effects of the processes that can cause discord between the speciation history and the individual gene histories into account has become evident. For multilocus datasets, it is difficult to achieve complete coverage of all sampled loci across all sample specimens, a problem that also arises when combining incompletely overlapping datasets. Here we examine how missing data affects the accuracy of species tree reconstruction. In our study, 10- and 100-locus sequence datasets were simulated under the coalescent model from shallow and deep speciation histories, and species trees were estimated using the maximum likelihood and Bayesian frameworks (with STEM and *BEAST, respectively). The accuracy of the estimated species trees was evaluated using the symmetric difference and the SPR distance. We examine the effects of sampling more than one individual per species, as well as the effects of different patterns of missing data (i.e., different amounts of missing data, which is represented among random taxa as opposed to being concentrated in specific taxa, as is often the case for empirical studies). Our general conclusion is that the species tree estimates are remarkably resilient to the effects of missing data. We find that for datasets with more limited numbers of loci, sampling more than one individual per species has the strongest effect on improving species tree accuracy when there is missing data, especially at higher degrees of missing data. For larger multilocus datasets (e.g., 25–100 loci), the amount of missing data has a negligible effect on species tree reconstruction, even at 50% missing data and a single sampled individual per species.

The teaching-learning process is analyzed in a course for a group of professors who were taught subjects on Calculus, to study the episodes of problem-solving in them, focused on the identification of patterns and argumentation using counterexamples. The explanation and the argument in the classroom can be used together so that the argument (issued as a counterexample) supports the explanation (conjecture). Developing the mathematics class so that the above occurs is a form of interaction and how to encourage students to move from explanation to argumentation (placing a hybrid system). Furthermore, both forms of reasoning can influence dialogue protocols and strategies. In this work, the dialogue model is described as a tool to address the problem that arises when working with students.

Preeclampsia (PE) is a pregnancy-specific disorder that affects 3 to 5% of pregnancies worldwide and is one of the leading causes of maternal and fetal morbidity and mortality. Nevertheless, how these events occur remains unclear. We hypothesized that the induction of hypoxic conditions in vitro in primary human trophoblast cells would mimic several characteristics of PE found in vivo. We applied and characterized a model of primary cytotrophoblasts isolated from healthy pregnancies that were placed under different oxygen concentrations: ambient O2 (5% pCO2, 21%pO2, 24 h, termed “normoxia”), low O2 concentration (5% pCO2, 1.5% pO2, 24 h, termed “hypoxia”), or “hypoxia/reoxygenation” (H/R: 6 h intervals of normoxia and hypoxia for 24 h). Various established preeclamptic markers were assessed in this cell model and compared to placental tissues obtained from PE pregnancies. Seventeen PE markers were analyzed by qPCR, and the protein secretion of soluble fms-like tyrosine kinase 1 (sFlT-1) and the placenta growth factor (PlGF) was determined by ELISA. Thirteen of seventeen genes associated with angiogenesis, the renin–angiotensin system, oxidative stress, endoplasmic reticulum stress, and the inflammasome complex were susceptible to H/R and hypoxia, mimicking the expression pattern of PE tissue. In cell culture supernatants, the secretion of sFlT-1 was increased in hypoxia, while PlGF release was significantly reduced in H/R and hypoxia. In the supernatants of our cell models, the sFlT-1/PlGF ratio in hypoxia and H/R was higher than 38, which is a strong indicator for PE in clinical practice. These results suggest that our cellular models reflect important pathological processes occurring in PE and are therefore suitable as PE in vitro models.